DNA Analysis of Tumor Tissue Samples From Patients With Human Papilloma Virus-Associated Cancer of the Oropharynx

Sponsor

Vanderbilt University Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT00897988

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

13.3

Patients Per Site

Study Details

Study Description

Brief Summary

RATIONALE: Studying samples of tumor tissue in the laboratory from patients with cancer may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer.

PURPOSE: This laboratory study is looking at the DNA in tumor tissue samples from patients with human papilloma virus-associated cancer of the oropharynx.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer	Genetic: gene expression analysis Genetic: mutation analysis Genetic: polyacrylamide gel electrophoresis Genetic: polymerase chain reaction Genetic: protein expression analysis Genetic: reverse transcriptase-polymerase chain reaction Other: flow cytometry Other: immunoenzyme technique Other: immunologic technique Other: laboratory biomarker analysis Other: pharmacological study

Detailed Description

OBJECTIVES:

Analyze PIK3CA expression and mutation and p110α amplification and expression in tumor tissue samples from patients with human papilloma virus positive (HPV+) and human papilloma virus negative (HPV-) squamous cell carcinoma (SCC) of the oropharynx.
Determine proliferation and survival after PI3K inhibition in HPV(+) and HPV(-) oropharyngeal SCC cell lines and in HPV E6 and E7 expressing cells.
Determine proliferation and survival after PI3K inhibition in short-term cultures of tumor tissue samples from patients with HPV(+) and HPV(-) primary SCC of the oropharynx.

OUTLINE: Previously collected tumor tissue samples are analyzed for HPV DNA by PCR amplification and direct sequencing of PCR products; expression of E6 protein and relative expression of PIK3CA by qRT-PCR; amplification of PIK3CA by Southern blotting; mutation of PIK3CA; expression of p110α, phospho-AKT, total AKT, and FOXO1 by polyacrylamide gel electrophoresis (PAGE) and immunoblotting; and the effect of PI3K inhibition on cell cycle and apoptosis by flow cytometry. Pharmacological studies are performed on oropharyngeal squamous cell carcinoma cell lines and short-term cultures and HPV E6 and E7 expressing cells using LY 294002 in vitro to analyze response to PI3K inhibition. Results of response to PI3K inhibition will be correlated with HPV status, PIK3CA expression, amplification, and mutation, and p110α expression.

PROJECTED ACCRUAL: A total of 20 HPV(+) and 20 HPV(-) tumor tissue specimens from patients will be accrued for this study.

Study Design

Study Type:

Observational

Anticipated Enrollment :

40 participants

Official Title:

Effect of PI3K Inhibition in HPV-Associated HNSCC

Study Start Date :

Apr 1, 2006

Outcome Measures

Primary Outcome Measures

PIK3CA expression and mutation and p110α amplification and expression in tumor tissue samples from patients with human papilloma virus positive (HPV+) and human papilloma virus negative (HPV-) squamous cell carcinoma (SCC) of the oropharynx []
Proliferation and survival after PI3K inhibition in HPV(+) and HPV(-) oropharyngeal SCC cell lines and in HPV E6 and E7 expressing cells []
Proliferation and survival after PI3K inhibition in short-term cultures of tumor tissues from patients with HPV(+) and HPV(-) primary SCC of the oropharynx []

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Undergoing operative procedures for biopsy and/or resection of squamous cell carcinoma (SCC) of the oropharynx
Tumor tissue sample available from the Head and Neck Tissue Repository and Clinical Database of Vanderbilt University
No tumors with human papilloma virus (HPV) DNA sequences but no expression of E6

PATIENT CHARACTERISTICS:

See Disease Characteristics

PRIOR CONCURRENT THERAPY:

Not specified

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vanderbilt-Ingram Cancer Center - Cool Springs	Nashville	Tennessee	United States	37064
2	Vanderbilt-Ingram Cancer Center at Franklin	Nashville	Tennessee	United States	37064
3	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232-6838